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Recent advances in drSH3 technology

Technology > Recent advances in drSH3 technology

Early work on SH3 targeting was based on Src-family SH3 domains Hck 1, 2 and Fyn 3, 4. More recent systematic analyses of the human SH3 repertoire by Next Biomed Therapies Oy have identified SH3 domains with categorically greater potential as targeting scaffolds.

Although all SH3 domains share a common fold, the presentation as well as the role upon folding of their unstructured loops differs between the human SH3 domains. This probably accounts for the unique suitability of the NPHP1 and Tec SH3 domains for combined RT- and n-src loop randomization, and the superior targeting potential of NPHP1- and Tec-based drSH3 scaffold libraries.

Based on extensive analyses regarding the optimal strategies for randomization of the ligand-binding loop structures in these SH3 domains Next Biomed Therapies Oy has generated extensive (size >1011) drSH3 phage display libraries, which show unprecedented potential for rapid selection of drSH3 domains binding to diverse targets of interest with high affinity.

See here for an example of optimized drSH3 library performance

drSH3 = double-randomized SH3

1. Hiipakka et al., (1999) J. Mol. Biol. 293, 1097–1106.
2. Hiipakka & Saksela (2007) FEBS Lett. 581, 1735–1741
3. Grabulovski et al., (2007) J. Biol. Chem. 282, 3196–3204
4. Schlatter et al. (2012) Mabs 4: 497-508